Skip to main content
main-content

28.11.2016 | Original Paper | Ausgabe 1/2017

Angiogenesis 1/2017

An exploratory association of polymorphisms in angiogenesis-related genes with susceptibility, clinical response and toxicity in gastrointestinal stromal tumors receiving sunitinib after imatinib failure

Zeitschrift:
Angiogenesis > Ausgabe 1/2017
Autoren:
Gloria Ravegnini, Margherita Nannini, Corrado Zenesini, Vittorio Simeon, Giulia Sammarini, Milena Urbini, Lidia Gatto, Maristella Saponara, Guido Biasco, Maria A. Pantaleo, Nicola Venturoli, Patrizia Hrelia, Sabrina Angelini
Wichtige Hinweise
Margherita Nannini and Corrado Zenesini have contributed equally to this work.
Patrizia Hrelia and Sabrina Angelini have jointly directed the study.

Abstract

The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls. Through a multiple candidate gene approach, we also investigated, for the first time, any possible significant associations with GIST susceptibility and clinical pathological features. The most important result shows two associations between polymorphisms in VEGFR3 rs6877011 (CC vs. CG, OR 9.7, 95% CI 3.31–28.4; P < 0.001) and rs7709359 (AA+AG vs. GG, OR 5.01, 95% CI 1.33–18.8; P = 0.017) and TTP. Interestingly, the association between VEGFR3 rs6877011 and TTP maintained the significance after applying the Bonferroni correction for multiple testing (P = 0.017). We also highlighted the association with sunitinib-related toxicity; in particular, VEGFA polymorphism rs3025039 (CT+TT vs. CC, OR 15.3, 95% CI 2.2–102.1; P = 0.005) is associated with severe toxicity, with the presence of the variant T allele associated with a grade ≥3 AE. Because of the small sample size and large number of tests performed, we cannot ignore the possibility that some associations have been retrieved by chance. However, the influence of VEGF polymorphisms in angiogenesis is a hypothesis worthy of exploration in cellular models and confirmation in a sizeable cohort of patients.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der Fachzeitschriften, inklusive eines Print-Abos.

Jetzt abonnieren und bis 25. Juni einen 50 € Amazon-Gutschein sichern.

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Supplementary material 1 (DOCX 27 kb)
10456_2016_9534_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

Angiogenesis 1/2017Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Kardiologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Kardiologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise